The goal of this project is to understand mechanisms of host defense and immunity against retroviruses. Previous work has defined several mouse genes which influence ability of mice to recover spontaneously from Friend virus complex (FV)-induced leukemia. Some of these genes also influence ability to induce protective immunity to this disease by vaccination with viral protein in adjuvants or expressed in recombinant vaccinia viruses. The most recent work has shown that protective immunity can be induced by both retroviral envelope and gag proteins expressed in vaccinia. Deletion of the amino or carboxy-termini of the gag polyprotein indicated that the amino-terminal half was responsible for the immune protection. This protection was weaker than that induced by the viral envelope protein, but it was successful in mice who were not capable of making a successful immune response to the envelope protein. These results suggested that both envelope and gag proteins should be considered as possible immunogens in constructing vaccines against other retroviruses. The mechanism of protection by immunization with gag protein is under further investigation.